Kyprolis® (Carfilzomib) Demonstrates Economic Value In Relapsed Or Refractory Multiple Myeloma Manuscript Published In "Journal of Medical Economics"

OREANDA-NEWS. May 27, 2016. Amgen (NASDAQ:AMGN) today announced that the Kyprolis Global Economic Model (K-GEM)¹ has been published in the Journal of Medical Economics showing that in the United States (U.S.), Kyprolis^® (carfilzomib) in combination with lenalidomide and dexamethasone (KRd) is cost-effective compared to lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma. The K-GEM demonstrated an incremental cost-effectiveness ratio of \\$107,250 per Quality-Adjusted Life Year (QALY). Kyprolis provides substantial value when its cost per QALY is contrasted against willingness-to-pay estimates of \\$150,000-\\$300,000 per QALY, which are cited as reasonable benchmarks for cancer in the U.S.^2-4  

"We recognize that there are different methods, assumptions and perspectives needed to assess the value of innovation," said

Joshua Ofman, M.D., M.S.H.S., senior vice president of Global Value and Access at Amgen. "The K-GEM was developed with input from experts worldwide as one of the multiple perspectives needed to assess value. Robust analysis, relying on clinical trial data to assess cost-effectiveness analysis is one approach that can help inform payer and provider decision-making related to value and costs.  Ultimately, individual patient treatment decisions for diseases like multiple myeloma should be made by doctors and their patients, based on sound clinical data and evidence-based practice guidelines."

"Each time a patient with multiple myeloma experiences a relapse, the ability to achieve and sustain a meaningful response to treatment declines, so we continue to seek better ways of treating patients with this complex disease.⁵ For the healthcare system, each relapse means the disease burden and cost of care increases," said Andrzej Jakubowiak, M.D., Ph.D., lead author of the manuscript. "The rigorous approach taken in the K-GEM demonstrates the economic value of the KRd regimen over standard of care, with clear evidence of compelling value for patients, payers and society."

The K-GEM incorporated data directly from a head-to-head Phase 3 trial (ASPIRE) in patients with relapsed or refractory multiple myeloma who had received one to three prior therapies. The ASPIRE trial showed that treatment with KRd resulted in a significant improvement (additional 8.6 months) in median progression-free survival (PFS) compared to Rd (26.3 months vs. 17.6 months, hazard ratio for progression or death = 0.69; 95 percent confidence interval [CI]: 0.57 to 0.83; p<0.0001).⁶ The most common adverse reactions leading to discontinuation in the KRd arm included pneumonia (1 percent), myocardial infarction (0.8 percent) and upper respiratory tract infection (0.8 percent). A critical assumption in economic models of cancer and also the K-GEM, where trial results have not matured sufficiently to fully characterize the extent of survival, is the extrapolation of overall survival. While a common evidence-based practice in health economics, it should not be considered a claim of extended survival.

About the Kyprolis Global Economic Model
The Kyprolis Global Economic Model (K-GEM) provides a robust framework for considering the value of Kyprolis in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. It was co-developed with experts worldwide over a number of years, and has been used as the basis for a number of statutory Health Technology Assessment analyses around the world. The K-GEM incorporated data directly from a comparative Phase 3 trial (ASPIRE) in patients with relapsed multiple myeloma who had received one to three prior therapies. 

About ASPIRE
The international, randomized Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial evaluated Kyprolis in combination with lenalidomide and dexamethasone (KRd), versus lenalidomide and dexamethasone (Rd) alone, in patients with relapsed multiple myeloma following treatment with one to three prior regimens.⁶ The primary endpoint of the trial was PFS, defined as the time from treatment initiation to disease progression or death.⁶ Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), disease control rate, health-related quality of life (HR-QoL) and safety.⁶ Patients were randomized to receive Kyprolis (20 mg/m2 on days 1 and 2 of cycle one only, escalating to 27 mg/m2 on days 8, 9, 15 and 16 of cycle one and continuing on days 1, 2, 8, 9, 15 and 16 of subsequent cycles), in addition to a standard dosing schedule of lenalidomide (25 mg per day for 21 days on, 7 days off) and low-dose dexamethasone (40 mg per week in four-week cycles), versus lenalidomide and low-dose dexamethasone alone.⁶ The study randomized 792 patients at sites in North America, Europe and Israel.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.⁷ It is a disease that, in 2012, accounted for approximately one percent of all cancers globally.^8,9 In the U.S., there were more than 95,000 people living with, or in remission from, multiple myeloma in 2013.¹⁰

About Amgen's Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen's supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

About Kyprolis^® (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.¹¹ Kyprolis has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.¹¹ In some cells, Kyprolis can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.^11,12 The irreversibility of Kyprolis' binding has also been shown to offer a more sustained inhibition of the targeted enzymes.¹²

Kyprolis is approved in the U.S. for the following:

• In combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
• As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Kyprolis is also approved in Argentina, Israel, Kuwait, Mexico, Thailand, Colombia, Korea, Canada, Switzerland and Russia and the European Union. Additional regulatory applications for Kyprolis are underway and have been submitted to health authorities worldwide.

For more information, please visit www.kyprolis.com.

Important Safety Information Regarding Kyprolis^® (carfilzomib) for Injection

INDICATION(S)

• KYPROLIS^® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
• KYPROLIS^® (carfilzomib) is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

• New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
• Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
• While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure.
• Patients > 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.

Acute Renal Failure

• Cases of acute renal failure and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

• Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved.

Pulmonary Toxicity

• Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.

Pulmonary Hypertension

• Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment.

Dyspnea

• Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart KYPROLIS based on a benefit/risk assessment.

Hypertension

• Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with KYPROLIS. Some of these events have been fatal. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment.

Venous Thrombosis

• Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient's underlying risks.
• Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with KYPROLIS in combination with dexamethasone or lenalidomide plus dexamethasone.

Infusion Reactions

• Infusion reactions, including life-threatening reactions, have occurred in patients receiving KYPROLIS. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.

Thrombocytopenia

• KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

• Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

• Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

• Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuroradiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known.

Embryo-fetal Toxicity

• KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.
• Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

ADVERSE REACTIONS

• The most common adverse events occurring in at least 20 percent of patients treated with KYPROLIS in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.
• The most common adverse events occurring in at least 20 percent of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see full Prescribing Information at www.kyprolis.com.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Forward-Looking Statement
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project.  Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market.

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CONTACT: Amgen, Thousand Oaks

Kristen Davis, 805-447-3008 (Media)

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